The research will investigate the role that biogenic aldehydes play in addiction to ethanol and other compounds. Studies of the enzyme responsible for formation and destruction of biogenic aldehydes at a basic level are proposed. Localization of the enzyme in the nervous system will be carried out. In particular, studies on the genetic basis and mechanism of increased liver aldehyde dehydrogenase activity produced by phenobarbital administration will be pursued. This information will be used to experimentally alter the steady state level of biogenic aldehydes in the body. Addiction to compounds which are predicted to increase brain biogenic aldehydes will be attempted in animals and compared to ethanol addiction. The studies are designed to provide a rational basis for the treatment of addiction to ethanol and other addictive drugs such as the barbiturates. BIBLIOGRAPHIC REFERENCES: Erwin, V. G., Heston, W. D. W., McClearn, G., nd Deitrich, R. A.: Effect of Hypnotic Agents on Mice with Differing Central Nervous System Sensitivity to Ethanol. Pharmacology, Biochemisty and Behavior. 4,679-683, 1977. Deitrich, R. A., Erwin, V. G., Troxell, P. A., ad Worth, W. S.: Inhibition of Aldehyde Dehydrogenase in Brain and Liver by Cyanamide. Biochemical Pharmacology. 25,2733-2737, 1976.